MST1R
protein-codingmacrophage stimulating 1 receptor, the group of CD molecules|IPT domain containing|Receptor tyrosine kinases
Gene summary
This gene encodes a cell surface receptor for macrophage-stimulating protein (MSP) with tyrosine kinase activity. The mature form of this protein is a heterodimer of disulfide-linked alpha and beta subunits, generated by proteolytic cleavage of a single-chain precursor. The beta subunit undergoes tyrosine phosphorylation upon stimulation by MSP. This protein is expressed on the ciliated epithelia of the mucociliary transport apparatus of the lung, and together with MSP, thought to be involved in host defense. Alternative splicing generates multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Jan 2016]
- RON
- PTK8
- SEA
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~17.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0014902
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MST1R variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002447.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 7 | 7 | 6 | 20 | ||
| missense | 1 | 204 | 20 | 6 | 231 | |
| nonsense | 3 | 2 | 5 | |||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 8 | 8 | ||||
| Total | 0 | 1 | 222 | 29 | 12 | 264 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002438.2 | 20 | MANE Select | |
| Ensembl | ENSP00000296474.3 | 20 | MANE Select | |
| RefSeq | NP_001231866.1 | 19 | Standard | |
| RefSeq | NP_001305842.1 | 18 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| mst1rb | Danio rerio | Structure: bone mineralization Quality: delayed abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signal Transduction
- Alpha6Beta4Integrin
- a6b1 and a6b4 Integrin signaling
- Signaling by MST1
- Signaling by Receptor Tyrosine Kinases
Biological Process
- defense response
- signal transduction
- transmembrane receptor protein tyrosine kinase signaling pathway
- single fertilization
- positive regulation of cell population proliferation
Molecular Function
- transmembrane receptor protein tyrosine kinase activity
- macrophage colony-stimulating factor receptor activity
- protein binding
- ATP binding
- Wnt-protein binding
Cellular Component
- stress fiber
- vacuole
- plasma membrane
- integral component of plasma membrane
- cell surface
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000296474
- Coding exons
- 20
- Length
- 16865
- Individuals with no LoFs
- 124993
- Homozygous LoFs
- 3
- Heterozygous LoFs
- 752
- Defined
- 125748
- p
- 0.00301
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.682 | 796 | 852 | 0.934 | 0.0000547 | 8943 |
| Missense (PolyPhen) | 268 | 296.26 | 0.90461 | 3292 | ||
| Synonymous | 1.41 | 326 | 360 | 0.905 | 0.0000229 | 3080 |
| Loss of Function | -0.0592 | 55 | 54.5 | 1.01 | 0.00000297 | 578 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.019 | 0.019 | notable |
| Latino/Admixed American | 0.0022 | 0.0022 | notable |
| Ashkenazi Jewish | 0.0022 | 0.0022 | notable |
| East Asian | 0.0015 | 0.0015 | notable |
| Finnish | 0.0023 | 0.0022 | notable |
| European (Non-Finnish) | 0.0020 | 0.0020 | notable |
| South Asian | 0.0018 | 0.0017 | notable |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to MST1 ligand. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces autophosphorylation of RON on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1 or the adapter GAB1. Recruitment of these downstream effectors by RON leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. RON signaling activates the wound healing response by promoting epithelial cell migration, proliferation as well as survival at the wound site. Plays also a role in the innate immune response by regulating the migration and phagocytic activity of macrophages. Alternatively, RON can also promote signals such as cell migration and proliferation in response to growth factors other than MST1 ligand. {ECO:0000269|PubMed:18836480, ECO:0000269|PubMed:7939629, ECO:0000269|PubMed:9764835}.;
- Disease
- DISEASE: Nasopharyngeal carcinoma, 3 (NPCA3) [MIM:617075]: A form of nasopharyngeal carcinoma, a malignant neoplasm that originates in the nasopharyngeal epithelium and includes 4 subtypes: keratinizing squamous cell, non-keratinizing, basaloid squamous cell, and papillary adenocarcinoma. {ECO:0000269|PubMed:26951679}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.154
Intolerance Scores
- LoFtool
- 0.857
- RVIS EVS
- -1.78
- RVIS percentile EVS
- 2.29
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.749
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |